Pancreatic cancer is the third leading cause of cancer death in the United States, with projections that it will become the second leading cause by the year 2030. It carries a dismal prognosis with a 5-year overall survival rate of less than 9% and is associated with numerous comorbidities, the most notable being cachexia. Defined as the loss of muscle mass not reversible by conventional nutritional support, cachexia is seen in over 85% of pancreatic cancer patients and contributes significantly to mortality, where nearly 30% of pancreatic cancer deaths are due to cachexia rather than tumor burden. Therefore, there is an urgent need to identify the mechanisms behind the development of muscle wasting in pancreatic cancer patients and design novel therapeutics targeting cachexia. This review highlights the current understanding surrounding the mechanisms underpinning the development of cachexia in pancreatic cancer, as well as the current mouse models of pancreatic cancer–induced muscle wasting described in the literature.